Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0000737 (abdominal pain)
 31,184 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).
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PMID:Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution. 898 Apr 9

Icodextrin is a glucose polymer obtained from starch hydrolysis. It is used as an osmotic agent at 7.5% for peritoneal dialysis (PD). Its use in PD has been associated with several side effects separate from the one reported here, the most frequent being sterile peritonitis. Recently, three mechanisms have been proposed to explain the occurrence of sterile peritonitis: allergy to dextrin, production of anti-dextran antibodies, and impurities introduced during manufacture. Here, we report a peritoneal mononucleosis outbreak that is highly suggestive of being a consequence of the last-mentioned mechanism. During the period December 2001 to May 2002, a group of 8 Spanish hospitals whose individual PD programs regularly share information and activity reported 29 cases of sterile peritonitis associated with icodextrin use in continuous ambulatory peritoneal dialysis (CAPD) patients [mean age: 60.7 +/- 14.47 years; 8 women (27.59%), 21 men (72.41%); mean time on PD: 25.21 +/- 35.31 months; mean time on icodextrin: 15.17 +/- 11.03 months]. Of the 29 patients, 51.8% showed no symptoms. The remainder presented with mild abdominal discomfort and anorexia. Only 2 patients showed general malaise, severe nausea, fever, and abdominal pain. The initial white cell count in peritoneal effluent was 512 +/- 386 cells/mL (45.0% +/- 28% neutrophils, 44.92% +/- 32.6% mono-nuclear cells, 7.75% +/- 12% eosinophils). In 5 of the patients, we performed an immunophenotype (CD14) study, demonstrating the monocyte nature of 60%-80% (mean: 70.6%) of the cells. Microbiology cultures were always negative. A rechallenge with the same batches of PD fluid was tried. In 100% of the patients, the clinical and cellular patterns relapsed. No short-term changes in peritoneal function have been observed. The manufacturer informed us that the icodextrin was contaminated with a peptidoglycan. In this sterile peritonitis outbreak with a simultaneous, similar clinical presentation in a group of patients treated with icodextrin solution (presumably contaminated with peptidoglycan), clinical outcome was, for the most part, mild-to-moderate. Symptoms disappeared immediately after icodextrin withdrawal and relapsed after rechallenge with the relevant fluid batches. Monocyte cell counts predominated during the episode. Although we cannot rule out an allergic cause, the massive peritoneal mononuclear cell recruitment suggests a particular mechanism. This is a new mechanism for peritoneal cell recruitment in PD.
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PMID:Severe peritoneal mononucleosis associated with icodextrin use in continuous ambulatory peritoneal dialysis. 1476 60